AbstractNutritional repletion of tumor‐bearing (TB) organisms by means of total parenteral nutrition (TPN) has been associated with gut atrophy, immunosuppression, and increased infection rate. To assess possible molecular mechanisms of intestinal atrophy during TPN, jejunal mucosal polyamine concentrations and biosynthetic activity were assessed in non‐TB (NTB) and TB rats maintained on rat chow or TPN for eight days. As expected, jejunal mucosal protein content was decreased in both groups of rats maintained on TPN. Although mucosal concentration of putrescine was decreased in TB groups and in the NTB group maintained on TPN, levels of spermidine and spermine were decreased only in the NTB‐TPN group. Spermidine levels were elevated significantly in both TB groups. The concentration of spermine was also elevated in the TB‐TPN group but was not changed in the TB group maintained on chow. Activity of ornithine decarboxylase was increased in the NTB‐TPN group but was not altered significantly in either TB group. S‐adenosylmethionine decarboxylase activity was decreased significantly in TB rats maintained on chow and was increased back to control level in the TB‐TPN group. These results suggest that jejunal mucosal polyamines are decreased in NTB rats maintained on TPN. Additionally, it appears that enzyme activity is induced in NTB‐TPN rats, perhaps in response to the reduction in polyamines and gut atrophy. The absence of similar changes in TB rats maintained on TPN suggests that regulatory mechanisms of polyamine biosynthesis, such as product inhibition, may be refractory. In addition, polyamine biosynthesis from other sources, such as tumor tissue, may be affecting the control of intestinal polyamine biosynthesis.